IS RELIEF RIGHT AROUND THE CORNER
FOR THE C.P. SUFFERER?

PART 2

For many patients who suffer from chronic pain, the complete refusal of most doctors to prescribe the only drugs that offer relief seems patronizing, if not downright cruel. Without adequate treatment, many consider suicide: It's a form of relief they do have access to, and at bad moments it can seem preferable to a life of persistent agony. "Nobody brought a gun today," jokes one man during a group session at the Mensana Clinic.

Faced with the desperation of their patients, a few doctors, particularly those at top pain clinics, have changed their minds about the use of narcotics for chronic pain. "Twenty years ago, I was strongly against the use of narcotics for chronic-pain patients," says Hendler. "My feeling, like most doctors, was there was potential for addiction. But Foley and Portenoy slowly and surely convinced me."

Still, pain specialists look forward to the day when there will be new and better pain-fighting drugs that allow them to rely less heavily on narcotics. To find such drugs, researchers have been delving into basic science, teasing apart the complex biology that underlies pain sensation.

The reason morphine works so well is that it taps into the body's own pain relief system. A painful impulse first travels from a broken finger, say, up the arm along a nerve leading into the spinal cord. There, a group of chemicals, called neurotransmitters, carry the information over a gap, or synapse, to a second nerve, which will ferry the message up the spine to the brain.

One class of these neurotransmitters is chemically similar to morphine. Like opioid drugs, these neurotransmitters, also called opioids, serve to blunt the pain signal as it moves from one neuron to the next.

Pain alert. In addition to the opioids, a slew of other neurotransmitters adjust the volume of pain intensity up or down before the brain ever finds out that something is wrong. Scientists still don't know exactly how this complicated process works. They do know that the nervous system has at least 15 different types of "receptors," each of which responds to one class of neurotransmitters. The presence of the right neurotransmitter tells a receptor to activate the nerve cell, changing the message it sends in some way. For example, the recently discovered "NMDA" receptor prompts nerve cells to be hypersensitive to pain, so that even a light touch can make a person scream.

NMDA and other pain enhancers may explain why morphine doesn't ease every patient's suffering. Researchers have recently found that the body sometimes responds to morphine by revving up pain enhancers like the NMDA system, which might be the body's effort to get the all-important pain message through to the brain. This may account for why many people need increasing doses of narcotics over time to obtain the same analgesic effect. And narcotics offer little relief for about half the people suffering from nerve damage, which often accompanies illnesses such as shingles, diabetes, cancer, AIDS, and some injuries like the one Bogan received. Researchers are not entirely sure why this is so, but they think it may occur because damaged nerves have fewer opioid receptors than healthy nerves, leaving no place for morphine molecules to dock.

In searching for better ways to treat pain, scientists have gained a greater appreciation of its utility. Pain is literally a lifesaver, alerting the brain to physical harm. "Pain is the body's smoke alarm," says Robert Coghill, a neurophysiologist at the National Institutes of Health. Victims of congenital analgesia, a rare condition that leaves them unable to feel pain, hurt themselves without knowing it, bending their joints to the point of tearing ligaments, or walking on a damaged bone until it breaks. They usually die by the time they are in their 30s from injuries they never felt, their bodies scarred from head to toe.

Because pain is so vital, the brain gives it priority over information coming in from other senses. New brain imaging techniques like Positron Emission Tomography">, or PET scanning, which give researchers a window on the brain's activity during pain, are showing that brain centers involved in everything from emotions, to movement, to attention "light up" in response to incoming pain signals. Such findings repudiate the notion that people in severe pain should "learn to live with it," says Hyman. "They can't. Pain makes us unhappy. This is hard-wired in the brain." A person in terrible, chronic pain curls into a ball of misery, his brain unable to pay attention to anything else.

This new understanding of how pain signals dominate the brain has solved a lot of mysteries. For example, scientists now know that pain literally rewires the brain and the nervous system, so that a pain can spread to parts of the body far from the original injury--something chronic patients know all too well but doctors have been slow to acknowledge. Recent studies show that when pain signals from a particular area of the body arrive in the spinal cord, neurons "recruit" neighboring nerve cells to respond as if they were receiving pain signals as well. In the lab, Coghill studies pain by injecting chili-pepper extract into the feet of volunteers. Although the extract penetrates only a tiny distance into the foot, he has observed that it can send searing pain shooting halfway up the subjects' legs. In a condition known as reflex sympathetic dystrophy, this kind of spreading pain never goes away, and sometimes it can eventually take over much of the body. This has taught researchers the importance of getting to pain early, before it leaves lasting impressions in the brain and nervous system. Dr. Charles Berde of Boston Children's Hospital has found one way to do just that. He places tiny capsules of anesthetic at nerve endings during surgery, which stop the patients' pain signals before they even start, and relieve pain for several days.

Such findings are pointing the way to new analgesics that will be able to manipulate the body's own mechanisms for transmitting pain. In recent studies, drugs that block NMDA's action can reduce tolerance to morphine. That means that eventually, patients will be able to get more relief with lower doses of opioids, and to avoid side effects like constipation.

Better chemistry. In the future, patients will be given drug cocktails, small amounts of four or five compounds that block different pain channels in the body. Several new classes of drugs used in various combinations are already in clinical trials, and a dozen new drugs are likely to reach the clinic within the next few years. And several drugs already in use for other purposes, such as antidepressants and anticonvulsants, are showing promise in treating pain.

Researchers are also looking for ways to rid patients of chronic pain while preserving the initial, brief burst of pain that alerts the brain to damage. For example, SNX-111, now in the final stages of clinical trials at Neurex Corp., interferes with a type of neuron dedicated solely to transmitting long-lasting pain.

It will take a while for these new drugs and techniques to reach those who suffer. In the meantime, the ongoing debate over the right to die is offering an opportunity--a chance to reconsider, to educate, to change rigid ways of thinking about pain. In some places, change is already happening. Over the last decade, doctors who specialize in treating terminal cancer patients have broken down some of the legal barriers and misperceptions that have traditionally hindered doctors from prescribing narcotics. And a new awareness of pain is appearing at medical schools and research institutions. Dartmouth Medical School, for example, is drafting a curriculum for teaching pain management and palliative care. And at the National Institutes of Health, a newly convened pain consortium will coordinate research now performed by far-flung scientific disciplines, and shepherd findings in basic science into commercial development.

Hospitals, too, are beginning to pay attention to pain. At the urging of the American Pain Society, some hospitals have begun to include a description of the patient's pain on the chart that records other vital signs, such as temperature and blood pressure. With a pain chart staring them in the face, nurses and doctors cannot avoid asking patients if they hurt, and they are more likely to take steps to control the pain. The Department of Health and Human Services has issued guidelines instructing hospitals to treat both chronic and acute pain aggressively with strong opioids. Though the guidelines are voluntary, millions of patients now refer to them when talking to their doctors about pain, says Dr. Daniel Carr, a co-author of the guidelines. "It's like raising the ocean an inch," he says. "It doesn't seem like much, but it can lead to massive changes."

Who will pay? Pain experts are heartened by the signs of improvement. But they worry that the cost-cutting fervor of insurance companies and HMOs will put limits on how much things can change. Treating pain can be expensive. An intrathecal morphine pump like Steinberg's, for example, can cost as much as $40,000. Doctors say they often have to spend weeks haggling for permission to prescribe pain-relieving drugs, technologies, or surgery, while their patients suffer.

Even more worrisome to pain specialists is the possibility that physician-assisted suicide will be legalized before better strategies for treating pain are in place. In the Netherlands, for example, where physician-assisted suicide and euthanasia were legalized 24 years ago, efforts to improve palliative care at the end of life remain undeveloped. The hospice movement there is more than 20 years behind its counterparts in the United States and Britain, where hospice doctors pioneered the use of narcotics for dying patients.

New drugs, new hospital policies, and a growing number of pain specialists may help bring about change. But what will finally persuade doctors and hospitals to alleviate unnecessary suffering is the realization by patients that they don't have to live with pain, and that dying is not the only solution. One day, severe pain could be a thing of the past, even at the end of life. "We're talking about having quality of life even in dying, and not having to spend the last three months of your life in total mismanagement," predicts Harold Slavkin, director of the National Institute of Dental Research. Within a few decades, more and more people will be living well, even into their 90s. They could also be dying well, free of pain.

Beth Brophy and Mary Brophy Marcus contributed to this report.